letrozole versus hmg in intrauterine insemination cycles h. jamal; h. serdaroglu; a. baysoy; e....

Letrozole versus hMG in Letrozole versus hMG in intrauterine insemination cyclesintrauterine insemination cycles

HH.. Jamal; Jamal; H. H. Serdaroglu; Serdaroglu; A. A.

Baysoy; Baysoy; E. E. KaKaratekelratekelii;; E. E. Attar; Attar; H. H.

OzornekOzornek

Istanbul, TurkeyIstanbul, Turkey

Aromatase Inhibitors

iii-Non-Steroid triazole group: Anastrazole, letrozole

i-Steroid group: Exemestane

ii-Non-Steroid imidazole group: Fadrozole.

letrozole

letrozole

reversible

Enhances ovarian response to gonadotropin stimulation

Increases endogenous

production of FSH

Increasing intraovarian androgen levels

Suppressing estrogen

Advantages of third-generation aromatase inhibitors

Extremely potent inhibition of aromataseVery specific inhibition of aromatase without significant inhibition of other steroidogenesis enzymes

Oral administration

100% bioavailability after oral administration

Rapid clearance from the body (short half-life, ~ 45 hours)No accumulation of the medications or their metabolitesNo significant active metabolites

Few mild adverse effects with high tolerability when given chronically

Few contraindications or drug interactions

Relatively inexpensive

IndicationsIndications

Ovulation induction

Breast cancer

Endometrial cancer

Endometriosis

uterine fibroids

a) Unexplained infertility

b) PCO

c) Poor responders

Cli

nica

l pre

gnan

cy r

ate

Human reproductionMitwally et al. 2003

0

5

10

15

20

25

Letrozole-FSH

CC-FSH FSH-only

IUI

19.1%18.7%

10.5%

Cli

nica

l pre

gnan

cy r

ate

Fertility and SterilityHealey et al. 2003

0

5

10

15

20

25

FSH FSH+Letrozole

IUI

20.9% 21.6%

A prospective randomized study comparing the results of intrauterine insemination (IUI) in women undergoing ovulation induction with either letrozole or Human Menopausal Gonadotropin (hMG).

ObjectiveObjective

Letrozole group

hMG group

IUI

80 couples

LETROZOLE GROUP(40 CASES)

hMG GROUP(40 CASES)

regular menstrual cycles

primary infertility

female age <36 years

All patients diagnosed as having unexplained infertility (lack of conception after at least 2 year of regular unprotected intercourse)

• Transvaginal ultrasound • Hormone profiles • Semen analysis

• Hysterosalpingogram • and/or Laparoscopy

normal normal

length of follicular phase endometrial

thickness

cost

premature LH

surge

14 mm follicles

clinical pregnancy rate

OHSS and multiple

pregnancy

Letrozole&

hMG

LH-surge was defined as an LH-surge was defined as an increase in LH level ≥increase in LH level ≥10100% 0%

over mean of preceding two days.over mean of preceding two days.

LH surge?

LetrozoleLetrozole vvs s hMGhMG

Day 3 Day 7

Day 3 Day 7

Letrozole 2x1

hMGhMG 1x75ıu (<30 years)

hMG 1x150ıu(30years)

HCGHCG

No luteal support was given.

IUI was performed by the same physician for all patients.

RESULTSRESULTS

Age (yrs)Age (yrs)

Duration of infertility (yrs)Duration of infertility (yrs)

baselinebaseline FSH (IU/l) FSH (IU/l)

baselinebaseline LH (IU/l) LH (IU/l)

baselinbaselin E E2 2 (pg/ml)(pg/ml)

LetrozoleLetrozole(n=(n=440)0)

2277.22±.22±55.5.5

55.3±.3±22.1.1

66.41±2.6.41±2.6

44.81±.81±44.5.5

39.54±139.54±12.2.00

hMGhMG(n=(n=4040))

28.1±4.328.1±4.3

55.9±.9±33.2.2

66.11±.11±11..77

5.29±5.29±22..11

441.74±1.74±1313.4.4

P: NSP: NS

LetrozoleLetrozole

[[4040]]

31.43±4.131.43±4.1

663.93.9 ± ± 41.3 41.3

59.759.7 ± ± 116.16.1

5522.9.9 ± ± 11.311.3

Semen parameters before preparation for insemination

RESULTSRESULTS

Age of male partner (yrs)Age of male partner (yrs)

ConcentrationConcentration

((xx101066/ml)/ml)

MMotility (%)otility (%)

Normal sperm forms (%)Normal sperm forms (%)

P valueP value

NSNS

NSNS

NSNS

NSNS

hMGhMG

[[4040]]

30.10±30.10±55.9.9

66.366.3 ± ± 44.444.4

662.42.4 ± 1 ± 15.35.3

54.154.1 ± ± 9.9.22

LetrozoleLetrozole

1122.77±.77±11..99

11.79±1.3.79±1.3

8.8.991±1±11.8.8

93.3%93.3%

1193.19±893.19±800

22

hMGhMG

1111..9090±±11.7.7

3.21±1.63.21±1.6

1010.05±.05±22..99

95.6%95.6%

875.15±3875.15±36868

22

Follicular Follicular pphasehase (days(days))

Follicle numberFollicle number

Endometrial Endometrial tthicknesshickness(mm)(mm)

Trilaminar patternTrilaminar pattern

HCG day E2HCG day E2

Premature luteinizationPremature luteinization

RESULTSRESULTS

P valueP value

NSNS

<<0.0010.001

NSNS

NSNS

<0.001<0.001

NSNS

LetrozoleLetrozole

17.5%17.5%

1(triplet)1(triplet)

00

hMGhMG

15 %15 %

1(twin)1(twin)

1(moderate1(moderate))

Pregnancy ratePregnancy rate

Multiple Multiple pregnancypregnancy

OHSSOHSS

RESULTSRESULTS

P P valuevalue

NSNS

NSNS

NSNS

The mean dose of hMG (mean number of ampoules/cycle) was 15.5 ampoules/cycle. While the dose of letrozole were stable (10 tablets/cycle). Letrozole had a cost of 43 $ per cycle while hMG was more costly with 225 $ per cycle.

Conclusion

• Although low estradiol levels and less number of mature follicles were obtained at the time of the hCG in the letrozole group, pregnancy rates were similar in both groups.

Conclusion• Another outcome we noticed that the stimulation

time lasted longer in the letrozole group. As other authors cited before that this longer time of stimulation may have beneficial effects on oocyte maturation and oocyte quality and this is maybe a reason that more pregnancies occured in the letrozole group.

Conclusion

• Despite significantly lower E2 levels in the letrozole-treated women, endometrial development was unaffected, endometrial thickness and pattern were similar in both groups.

Conclusion

• Serious complications (OHSS, multiple pregnancy) were rare in the two groups. Low estradiol levels and less number of mature follicles at the time of the hCG in the letrozole group may be a reason to minimize and thereby avoid the complications of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. But to compare such an outcome, a large study including a very large number of patients must be required.

letrozole

efficient cost effective

simple and convenient

Thanks!